Chan Y M, Bönnemann C G, Lidov H G, Kunkel L M
Howard Hughes Medical Institute, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
J Cell Biol. 1998 Dec 28;143(7):2033-44. doi: 10.1083/jcb.143.7.2033.
The sarcoglycans are a complex of four transmembrane proteins (alpha, beta, gamma, and delta) which are primarily expressed in skeletal muscle and are closely associated with dystrophin and the dystroglycans in the muscle membrane. Mutations in the sarcoglycans are responsible for four autosomal recessive forms of muscular dystrophy. The function and the organization of the sarcoglycan complex are unknown. We have used coimmunoprecipitation and in vivo cross-linking techniques to analyze the sarcoglycan complex in cultured mouse myotubes. We demonstrate that the interaction between beta- and delta-sarcoglycan is resistant to high concentrations of SDS and alpha-sarcoglycan is less tightly associated with other members of the complex. Cross-linking experiments show that beta-, gamma-, and delta-sarcoglycan are in close proximity to one another and that delta-sarcoglycan can be cross-linked to the dystroglycan complex. In addition, three of the sarcoglycans (beta, gamma, and delta) are shown to form intramolecular disulfide bonds. These studies further our knowledge of the structure of the sarcoglycan complex. Our proposed model of their interactions helps to explain some of the emerging data on the consequences of mutations in the individual sarcoglycans, their effect on the complex, and potentially the clinical course of muscular dystrophies.
肌聚糖是由四种跨膜蛋白（α、β、γ和δ）组成的复合体，主要在骨骼肌中表达，并与肌膜中的抗肌萎缩蛋白和肌营养不良聚糖紧密相关。肌聚糖的突变是导致四种常染色体隐性遗传性肌营养不良症的原因。肌聚糖复合体的功能和组织结构尚不清楚。我们运用免疫共沉淀和体内交联技术，对培养的小鼠肌管中的肌聚糖复合体进行了分析。我们证明，β-肌聚糖和δ-肌聚糖之间的相互作用对高浓度的十二烷基硫酸钠具有抗性，而α-肌聚糖与该复合体的其他成员结合得不太紧密。交联实验表明，β-、γ-和δ-肌聚糖彼此紧邻，且δ-肌聚糖能够与肌营养不良聚糖复合体交联。此外，三种肌聚糖（β、γ和δ）显示形成了分子内二硫键。这些研究增进了我们对肌聚糖复合体结构的了解。我们提出的它们之间相互作用的模型，有助于解释有关各个肌聚糖突变的后果、其对复合体的影响以及潜在的肌营养不良症临床病程的一些新出现的数据。
